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Protein

Proprotein convertase subtilisin/kexin type 4

Gene

Pcsk4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (By similarity). May also participate in folliculogenesis in the ovaries (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei155Charge relay systemBy similarity1
Active sitei196Charge relay systemBy similarity1
Active sitei370Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.B25. 5301.

Protein family/group databases

MEROPSiS08.074.

Names & Taxonomyi

Protein namesi
Recommended name:
Proprotein convertase subtilisin/kexin type 4 (EC:3.4.21.-)
Short name:
PC4
Alternative name(s):
KEX2-like endoprotease 3
Neuroendocrine convertase 3
Short name:
NEC 3
Prohormone convertase 3
Gene namesi
Name:Pcsk4
Synonyms:Nec-3, Nec3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620325. Pcsk4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
PropeptideiPRO_000002710027 – 110Sequence analysisAdd BLAST84
ChainiPRO_0000027101111 – 678Proprotein convertase subtilisin/kexin type 4Add BLAST568

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi472N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.By similarity
Synthesized in the endoplasmic reticulum as a zymogen, is matured by autocatalytic cleavage between the prodomain and the catalytic domain.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ78EH2.
PRIDEiQ78EH2.

Expressioni

Tissue specificityi

Expressed abundantly in the testis. High levels seen in germ cells but not in Leydig, Sertoli or peritubular cells. Expressed in the pachytene spermatocytes and the round spermatids but not in the elongating spermatids. May be expressed within hormonally stimulated ovaries.1 Publication

Developmental stagei

First expressed postnatally between days 19 and 22 coinciding with the early stages of spermiogenesis. The levels increase up to postnatal day 60.1 Publication

Interactioni

Subunit structurei

The proPCSK4 form interacts with HSPA5; the interaction takes place at the endoplasmic reticulum.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022358.

Structurei

3D structure databases

ProteinModelPortaliQ78EH2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini150 – 436Peptidase S8Add BLAST287

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ78EH2.
KOiK08671.
PhylomeDBiQ78EH2.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR008979. Galactose-bd-like.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q78EH2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRPSQTALWL GLVLSLALLA VGWASARPPI YVSSWAVRVT KGYQEAERLA
60 70 80 90 100
RKFGFVNLGQ IFPDDQYFHL RHRGVAQQSL TPHWGHRLRL KKEPKVRWFE
110 120 130 140 150
QQTLRRRVKR SLVVPTDPWF SKQWYMNKEI EQDLNILKVW NQGLTGRGVV
160 170 180 190 200
VSILDDGIEK DHPDLWANYD PLASYDFNDY DPDPQPRYTP NDENRHGTRC
210 220 230 240 250
AGEVSATANN GFCGAGVAFN ARIGGVRMLD GAITDIVEAQ SLSLQPQHIH
260 270 280 290 300
IYSASWGPED DGRTVDGPGL LTQEAFRRGV TKGRQGLGTL FIWASGNGGL
310 320 330 340 350
HYDNCNCDGY TNSIHTLSVG STTRQGRVPW YSEACASTFT TTFSSGVVTD
360 370 380 390 400
PQIVTTDLHH QCTDKHTGTS ASAPLAAGMI ALALEANPLL TWRDLQHLVV
410 420 430 440 450
RASRPAQLQA EDWRINGVGR QVSHHYGYGL LDAGLLVDLA RVWLPTKPQK
460 470 480 490 500
KCTIRVVHTP TPILPRMLVP KNVTVCCDGS RRRLIRSLEH VQVQLSLSYS
510 520 530 540 550
RRGDLEIFLT SPMGTRSTLV AIRPLDISGQ GYNNWIFMST HYWDEDPQGL
560 570 580 590 600
WTLGLENKGY YYNTGTLYYC TLLLYGTAED MTARPQTPQE SHCPLSIVAE
610 620 630 640 650
LCLISSKQWW WLYSHTQQPV TKGQDSCHPP TTPARQLDQR LHCLFPAPHA
660 670
GSASEPLQGL SPLAAILAIS LGPWCCPC
Length:678
Mass (Da):75,740
Last modified:July 5, 2004 - v1
Checksum:iBB5C7DC1BD19E6BA
GO
Isoform 2 (identifier: Q78EH2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     590-599: Missing.

Show »
Length:668
Mass (Da):74,703
Checksum:iA1696F8F1623BB75
GO
Isoform 3 (identifier: Q78EH2-3) [UniParc]FASTAAdd to basket
Also known as: rPC4-A

The sequence of this isoform differs from the canonical sequence as follows:
     590-678: ESHCPLSIVA...ISLGPWCCPC → VTSCAHACAE...SPSYHTCSAA

Show »
Length:654
Mass (Da):72,597
Checksum:iE2003798419DEAAD
GO
Isoform 4 (identifier: Q78EH2-4) [UniParc]FASTAAdd to basket
Also known as: rPC4-B

The sequence of this isoform differs from the canonical sequence as follows:
     590-678: ESHCPLSIVA...ISLGPWCCPC → KVIVPSPLWQNSASSPASSGGGSTATHSSQ

Show »
Length:619
Mass (Da):68,953
Checksum:i8D9B0EB519E60252
GO
Isoform 5 (identifier: Q78EH2-5) [UniParc]FASTAAdd to basket
Also known as: rPC4-C

The sequence of this isoform differs from the canonical sequence as follows:
     590-678: ESHCPLSIVA...ISLGPWCCPC → NSASSPASSGGGSTATHSSQ

Show »
Length:609
Mass (Da):67,805
Checksum:i0F07B718538E718B
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011274590 – 678ESHCP…WCCPC → VTSCAHACAEGHRGAVPGKS LSPLHCGRTLPHLQQAVVVA LQPHTAASDQGTGQLSPSYH TCSAA in isoform 3. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_011275590 – 678ESHCP…WCCPC → KVIVPSPLWQNSASSPASSG GGSTATHSSQ in isoform 4. 2 PublicationsAdd BLAST89
Alternative sequenceiVSP_011276590 – 678ESHCP…WCCPC → NSASSPASSGGGSTATHSSQ in isoform 5. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_011273590 – 599Missing in isoform 2. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14937 mRNA. Translation: AAA41814.1.
L14937 mRNA. Translation: AAA41815.1.
L14937 mRNA. Translation: AAA41816.1.
BC097288 mRNA. Translation: AAH97288.1.
PIRiA45357.
RefSeqiNP_598243.1. NM_133559.1. [Q78EH2-3]
UniGeneiRn.2899.

Genome annotation databases

GeneIDi171085.
KEGGirno:171085.
UCSCiRGD:620325. rat. [Q78EH2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14937 mRNA. Translation: AAA41814.1.
L14937 mRNA. Translation: AAA41815.1.
L14937 mRNA. Translation: AAA41816.1.
BC097288 mRNA. Translation: AAH97288.1.
PIRiA45357.
RefSeqiNP_598243.1. NM_133559.1. [Q78EH2-3]
UniGeneiRn.2899.

3D structure databases

ProteinModelPortaliQ78EH2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022358.

Protein family/group databases

MEROPSiS08.074.

Proteomic databases

PaxDbiQ78EH2.
PRIDEiQ78EH2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi171085.
KEGGirno:171085.
UCSCiRGD:620325. rat. [Q78EH2-1]

Organism-specific databases

CTDi54760.
RGDi620325. Pcsk4.

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ78EH2.
KOiK08671.
PhylomeDBiQ78EH2.

Enzyme and pathway databases

BRENDAi3.4.21.B25. 5301.

Miscellaneous databases

PROiQ78EH2.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR008979. Galactose-bd-like.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPCSK4_RAT
AccessioniPrimary (citable) accession number: Q78EH2
Secondary accession number(s): A1A4C9, Q07213, Q07214
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: November 2, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.